Table 2.

Disorders to Consider in the Differential Diagnosis of Marinesco-Sjögren Syndrome (MSS)

DiffDx DisorderGene(s)MOIClinical Features of DiffDx Disorder
Overlapping with MSSDistinguishing from MSS
Congenital cataracts, facial dysmorphism, and neuropathy syndrome (CCFDN) 1 CTDP1 AR
  • Cataracts
  • DD
  • Short stature
  • Hypogonadism
  • Absence of cerebellar atrophy & myopathy
  • Presence of hypo- or demyelinating neuropathy & post-infectious rhabdomyolysis
GBA2-related Marinesco-Sjögren syndrome-like disorder 2 GBA2 AR
  • Ataxia developing in early childhood
  • Normal early psychomotor development; however, mild progressive cognitive decline accompanies the other progressive CNS findings.
  • Bilateral cataracts observed later in disease course.
  • Lower-limb spasticity
  • Axonal peripheral neuropathy
  • Significantly ↑ concentrations of glucosylceramide in both erythrocytes & plasma
VLDLR-associated cerebellar hypoplasia VLDLR AR
  • Congenital ataxia predominantly truncal, → delayed ambulation
  • Cerebellar atrophy
  • Moderate-to-profound ID
  • Dysarthria
  • Strabismus
  • Non-progressive clinical course
  • Absence of progressive myopathy & ↑ serum creatine kinase concentration characteristic of MSS
Cerebral amyloid angiopathy, ITM2B-related, 2 (OMIM 117300) ITM2B AD
  • Cataracts
  • Ataxia
  • Absence of symptoms in childhood
  • Absence of cerebellar atrophy
  • Cataracts & ataxia later in onset than in MSS
  • Presence of dementia (or psychosis)
Muscular dystrophy, congenital, w/cataracts & ID (OMIM 617404) INPP5K AR
  • Myopathy, muscle weakness, & hypotonia
  • Cataracts
  • Strabismus
  • Short stature
  • Normal findings on brain MRI, absence of cerebellar atrophy
  • Absence of ataxia
Mitochondrial disorders (See Mitochondrial Disorders Overview.)
  • Myopathy
  • Cerebellar atrophy & ataxia
  • Encephalopathy, seizures, dementia, migraine, & stroke-like episodes often present
  • ↑ concentration of lactate
  • Cardiomyopathy

AD = autosomal dominant; AR = autosomal recessive; CNS = central nervous system; DD = developmental delay; DiffDx = differential diagnosis; ID = intellectual disability; MOI = mode of inheritance

1.

To date, CCFDN has only been reported in persons of Roma ethnicity.

2.

From: Marinesco-Sjögren Syndrome

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